Acute excess caloric intake negatively affects the rhythmic expression of the human growth hormone gene and its association with the circadian‐linked transcription factor Bmal1
Bibliographic record
Abstract
Rhythmicity of biological functions is fundamental for optimal adaptations to environmental cues. Growth hormone (GH) is a major metabolic homeostatic factor that is secreted with a circadian pattern, but whether it is produced rhythmically is unknown. We used transgenic (TG) mice containing the intact human GH gene locus (human GH/CS‐TG) to investigate the rhythmicity of human GH gene ( hGH‐N ) expression. Human GH RNA expression oscillates over a 24‐hour cycle. Moreover, we have previously reported that excess caloric intake is associated with a decrease in human GH synthesis with reduced hGH‐N promoter function. Sequence analysis of the hGH‐N promoter revealed the presence of an enhancer motif (E‐box) and as such a putative binding site for circadian transcriptional machinery (Bmal1 and Clock). Results from electrophoretic mobility shift assay support participation of Bmal1/Clock and the hGH‐N E‐box DNA element in a common complex. Transfection studies combined with site‐directed mutagenesis revealed that this E‐box DNA element contributes to basal hGH‐N promoter activity. Furthermore, Bmal1/Clock were able to trans activate the hGH‐N promoter. The ability of Bmal1 to associate with the hGH‐N promoter region containing the E‐box element was confirmed in the human GH/CS‐TG mouse pituitary in situ by chromatin immunoprecipitation assay. Occupancy was reduced in mice fed a high fat diet during the light cycle. This decrease was not seen, however, during the dark cycle. Initial assessment of the mechanism suggests an impact of excess caloric intake on the chromatin and/or DNA structure. In summary, the presence of an E‐box DNA element as well as association of Bmal1 with the hGH‐N promoter region in situ supports the notion that hGH‐N is a cyclic gene. Acute excess caloric intake for three days was sufficient to reprogram the circadian rhythm mediated by chromatin remodeling of the hGH‐N promoter region and interfer with recruitment of Bmal1 to the E‐box element. Further investigation of the rhythmic expression of human GH may provide insight into the changes in GH availability under pathophysiological conditions such as metabolic changes associated with overeating and obesity. Support or Funding Information Funded by the Canadian Institutes of Health Research
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".